Cardiovascular and lumenal stents are highly effective in the treatment of heart disease and other vascular conditions by the dilation and retention of constricted vessels or bodily conduits. However, their insertion may induce undesirable bodily reactions such as inflammation, infections, thrombosis or blood clots, restenosis, and proliferation of cell growth that occludes the passageway and may incur the need for additional surgery. Pharmaceutical drugs and compounds may assist in preventing these conditions, although they may be required in large oral or intravenous doses with stringent intake or injection timetables to increase their efficacy.
Pharmaceutical compounds may be coated directly on the stent to provide a preferable point-of-use drug delivery system, but these coatings must be bioengineered to control the release of sometimes highly potent and potentially toxic drugs. Timed-release attributes of a coating must be incorporated to avoid clinically unacceptable premature releases of toxic levels of potent drugs. Biocompatible, biodegradable polymers for various biomedical applications such as those used in sutures and tissue engineering have been described in “Functionalized Polyester Graft Copolymers,” Hrkach, et al., U.S. Pat. No. 5,654,381, issued Aug. 5, 1997. Drug-polymers based on polylactide and drug mixtures in particle or pellet form to provide timed-release delivery are described in “Polylactide-Drug Mixtures,” Boswell, et al., U.S. Pat. No. 3,773,919, issued Nov. 20, 1973, or in a spray form as described in “Polylactide-Drug Mixtures for Topical Application,” Scribner, et al., U.S. Pat. No. 3,755,558, issued Aug. 28, 1973. Reducing the water solubility of pharmaceutical compounds has been recognized as a technique for enhancing timed-release attributes of the compounds. A composition for administration of a paclitaxel derivative with a water solubility less than that of paclitaxel and its incorporation into a suitable polymeric carrier including a stent formed from the polymer has been described in “Composition and Methods for Administration of Water-insoluble Paclitaxel Derivatives,” Alvarado, et al., international publication number WO 00/41687, published Jul. 20, 2000. Drugs contained within a polymeric matrix for inhibiting stenosis following vascular trauma are presented in “Therapeutic Inhibitor of Vascular Smooth Muscle Cells,” L. Kunz, international publication number WO 94/07529, published Apr. 14, 1994. A polymeric coating on a stent including two layers, the outer layer being a surface erodable polymer and an inner layer including a drug, is described in “Stents Having Multiple Layers of Biodegradable Polymeric Composition,” Wang, et al, international publication number WO 98/56312, published Dec. 17, 1998.
These developments in pharmaceutical coatings, however, have limited control over the delivery of the drug and versatility in the types of drugs to be delivered and their pharmacodynamics. The delivery of the drug may be too fast, ineffective and possibly toxic, or too slow and ineffective. The drug coating may not stick or adhere. The drug polymer coatings should coat the stent framework without cracking, peeling or delaminating, particularly when the stent is expanded during installation. The coating should not fall off, crack, fracture, crystallize or melt during processing, sterilizing, or installing. In some cases, a rapid delivery of a drug may be needed immediately following surgery, followed by a steady delivery of the drug at a lesser rate over an extended period of time. Because there is need for the in vivo delivery of more than one drug, delivery of one or multiple drug types from a deployed, coated stent with variable elution rates is desirable. One drug type in a polymer coating may elute faster than another drug type in the same polymer, thus methods of modulating a drug without impacting its bioactive moiety are desirable.
An object of the current invention is to tailor a bioactive agent such as a drug in a pharmacologically unaltered way for controlled delivery from a stent coating, and to provide a drug-polymer system that can be tailored to the desired elution rate for a specific bioactive agent. Another objective is to modulate a bioactive agent and interdisperse the bioactive agent within a polymer matrix for controlled delivery from the stent coating. Another objective is to modify a polymer coating with a bioactive agent or pharmaceutical drug and coat the stent for controlled, timed release from the stent. Another objective is to provide a robust stent coating to survive expansion of the stent, whether by balloon expansion or by self-expansion. Another object is to provide a means for drug delivery from an endovascular stent with desired, timed-release properties.
It is a further object of this invention, therefore, to provide a method and system for treating heart disease, cardiovascular ailments and other vascular conditions utilizing catheter-delivered stents, as well as overcome the obstacles described above.